Chemical definition of the serum anaphylataxins has progressed rapidly in recent years and structure-function studies are proposed here to further define the active site and mechanisms of action of these factors. Anaphylatoxins are low molecular weight polypeptides released from complement components in the course of complement activation. Complete primary structures of two human anaphylatoxins (e.g. C3a and C5a) have recently been elucidated in my laboratory. Quantitative data has also been collected regarding numerous biological activities associated with these purified anaphylatoxins in assays designed to assess their actions both in vitro and in vivo. Two additional humoral factors, human C4a and C3e, will be examined both chemically and biologically as proposed here in. Recently C4a has been shown to exhibit anaphylatoxin-like activity and C3e is reportedly a potent leukocyte mobilizing factor. Chemical analysis of human C4a will contribute phylogenetic information pertaining to the origins of the entire complement systems as well as provide insight into the basis of its biological activity. The structure-function relationships of C3e are entirely unknown and therefore characterization at the molecular level will contribute a deeper understanding of the functional nature of this unusual C3 fragment. It is just now feasible to approach the difficult problems of estimating the role of complement-derived humoral factors in target tissues such as the lung. Studies dealing with the lung will involve influences of C3a, C3e, C4a or C5a on brochiolar constriction, vascular changes in lung tissue (e.g. edema induction, vasoconstriction and permeability changes) and possible release reactions occurring in the lung. Cellular effects such as C5a-induced chemotaxis dictate detailed measurements of cellular activity in the lung. These studies will be undertaken with particular emphasis on PMN sequestration and alveolar macrophage stimulation. Tools such as the purified humoral factors, modified factors and derivatives, specific antibodies to the factors (synthetic inhibitors) and synthetic analogs will all be used to examine the mechanisms of action of anaphylatoxic and chemotactic effects in lung tissue. Ultimately, the goal is to understand the role played by humoral mediators such as the anaphylatoxins in inflammatory processes.